Innate immunity and HCV Markus H. Heim  Journal of Hepatology  Volume 58, Issue 3, Pages 564-574 (March 2013) DOI: 10.1016/j.jhep.2012.10.005 Copyright © 2012 European Association for the Study of the Liver Terms and Conditions

Fig. 1 IFN signaling through the Jak-STAT pathway. Type I (IFN-αs and IFN-β) and type III (IFN-λs) IFNs bind to distinct receptors, but activate the same downstream signaling events, and induce almost identical sets of genes mainly through the activation of IFN-stimulated gene factor 3 (ISGF3) and STAT1 homodimers. IFN-γ (the only type II IFN) activates STAT1, but not ISGF3, and induces a partially overlapping but distinct set of genes. Adapted from Ref. [116], with permission from Elsevier. Journal of Hepatology 2013 58, 564-574DOI: (10.1016/j.jhep.2012.10.005) Copyright © 2012 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Natural course of HCV infection. In the early phase of acute infection (the first 4–8weeks), HCV induces a type I or III IFN response that restricts viral replication (green box). With the recruitment of HCV specific T cells in the late phase of AHC, the gene expression profile in the liver switches to an IFN-γ pattern (blue box). In late AHC, viral replication is strongly inhibited, and in about 30% of the patients, HCV is completely eliminated. In 70% of the cases, HCV persists and can induce again a type I or III IFN response in about half of the patients (upper green box). The other patients have little to no activation of ISGs in the liver (empty box). Changes in serum HCV load (red), alanine aminotransferase levels (ALT) (blue) and IFN-stimulated gene expression (top bar) are shown. The dashed line shows the upper limit of normal for ALT. Adapted from Ref. [116], with permission from Elsevier. Journal of Hepatology 2013 58, 564-574DOI: (10.1016/j.jhep.2012.10.005) Copyright © 2012 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Treatment of chronic hepatitis C with PegIFN-α and ribavirin. Patients with an activated endogenous IFN system have hundreds of ISGs upregulated already before treatment (light green). Application of PegIFN-α does not further increase ISG expression in the liver and continuous treatment with PegIFN-α and ribavirin rarely achieves a sustained virological response (light red line). Patients without a pre-activated IFN system show a massive induction of ISGs within 4h after administration of PegIFN-α (dark green), and have a high chance of being cured by PegIFN-α/ribavirin therapy (dark red line). Adapted from Ref. [116], with permission from Elsevier. Journal of Hepatology 2013 58, 564-574DOI: (10.1016/j.jhep.2012.10.005) Copyright © 2012 European Association for the Study of the Liver Terms and Conditions

Fig. 4 IL28B gene locus on human chromosome 19. The 3 most strongly associated SNPs are in the genome regions flanking the IL28B gene. Nucleotide numbers on chromosome 19 are indicated for three SNPs and for the start of the coding region of the IL28A and IL28B gene. Adapted from Ref. [116], with permission from Elsevier. Journal of Hepatology 2013 58, 564-574DOI: (10.1016/j.jhep.2012.10.005) Copyright © 2012 European Association for the Study of the Liver Terms and Conditions

Journal of Hepatology 2013 58, 564-574DOI: (10. 1016/j. jhep. 2012. 10 Copyright © 2012 European Association for the Study of the Liver Terms and Conditions

Journal of Hepatology 2013 58, 564-574DOI: (10. 1016/j. jhep. 2012. 10 Copyright © 2012 European Association for the Study of the Liver Terms and Conditions

Journal of Hepatology 2013 58, 564-574DOI: (10. 1016/j. jhep. 2012. 10 Copyright © 2012 European Association for the Study of the Liver Terms and Conditions